thalidomide, prednisone, and cyclophosphamide in treating patients with myelofibrosis and myeloid metaplasia

Conditions: Chronic Myeloproliferative Disorders; Secondary Myelofibrosis

Summary: rationale: giving thalidomide together with prednisone and cyclophosphamide may lessen symptoms caused by myelofibrosis and myeloid metaplasia. purpose: this phase ii trial is studying the side effects and how well giving thalidomide together with prednisone and cyclophosphamide works in treating patients with myelofibrosis and myeloid metaplasia.

objectives: primary * determine the benefit of thalidomide, prednisone, and cyclophosphamide in alleviating disease-associated anemia, thrombocytopenia, and/or splenomegaly in patients with myelofibrosis with myeloid metaplasia (mmm). * determine the benefit of this regimen in palliating four hypercatabolic constitutional symptoms (i.e., weight loss, fatigue, drenching night sweats, and unexplained fevers) in these patients. * determine the toxicity profile of this regimen in these patients. secondary * determine the effect of this regimen on leukocyte count. * determine the effect of this regimen on bone marrow histology, including microvessel density and reticulin fibrosis. * determine the effect of this regimen on intramedullary and urinary markers of angiogenesis. * determine the effect of this regimen on circulating myeloid progenitor cells by quantifying cd34+ cells. outline: patients receive oral thalidomide, oral prednisone, and oral cyclophosphamide (tpc) once daily on days 1-28. treatment repeats every 28 days for 3 courses. after 3 courses (3 months) of treatment, patients who respond to tpc therapy may receive oral thalidomide alone once daily for up to 3 months in the absence of disease progression or unacceptable toxicity. patients undergo bone marrow aspirate and biopsy prior to study entry, 6 months after starting therapy, and then every 6 months for up to 3 years. samples are analyzed by microvessel density/angiogenesis studies (i.e., cd34 immunohistochemical and vascular endothelium-specific staining) to determine the effect of therapy on markers of bone marrow angiogenesis. after completion of study therapy, patients are followed every 6 months for up to 3 years. projected accrual: a total of 22 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * histologically confirmed myelofibrosis with myeloid metaplasia (mmm) of any of the following subtypes: * agnogenic myeloid metaplasia * post-polycythemic myeloid metaplasia * post-thrombocythemic myeloid metaplasia * must have 1 of the following mmm-related conditions: * anemia, defined as hemoglobin \< 10 g/dl * iron deficiency must be excluded as cause * thrombocytopenia, defined as platelet count \< 100,000/mm³ * palpable hepatomegaly or splenomegaly * no evidence of myelofibrosis-associated conditions in the bone marrow, including any of the following: * metastatic carcinoma * lymphoma * myelodysplasia * hairy cell leukemia * mast cell disease * acute leukemia (including m7 type) * acute myelofibrosis * no chromosomal translocation t(9:22) or bcr-abl as determined by bone marrow chromosome analysis or peripheral blood fluorescent in situ hybridization (fish) analysis patient characteristics: * ecog performance status 0-3 * absolute neutrophil count ≥ 750/mm³ * bilirubin ≤ 2 times upper limit of normal (uln), unless elevation due to mmm * ast ≤ 5 times uln, unless elevation due to mmm * creatinine ≤ 2.5 mg/dl * no uncontrolled infection, including tuberculosis * no known history of positive purified protein derivative (ppd) untreated by isoniazid therapy * positive ppd with normal chest x-ray and completion of full-course isoniazid therapy allowed * no federal medical center inmates or other incarcerated patients * no peripheral neuropathy ≥ grade 2 * no comorbid condition in which the use of study therapy is felt to be potentially harmful * not pregnant or nursing * negative pregnancy test * fertile patients must use 2 forms of effective contraception prior concurrent therapy: * no chemotherapy (e.g., hydroxyurea, myelosuppressive therapy) within the past 14 days * prior splenectomy for mmm allowed * no concurrent hematopoietic growth factors

Keywords: primary myelofibrosis essential thrombocythemia polycythemia vera secondary myelofibrosis